Sucralfate is, chemically, sucrose octakis(hydrogen sulfate) aluminum complex. When ingested, the complex adheres to ulcer surfaces in the gastrointestinal track, thereby shielding the ulcerated site from further destructive action by the digestive content of the track. The usual dose is 1 gram of sucralfate four times per day.
U.S. Pat. No. 3,432,489 describes the general synthesis of various disaccharide polysulfates and, therefrom, their aluminum complexes together with their relative therapeutic utilities. The reference, more specifically, describes the reaction of sucrose with many sulfating agents including chlorosulfonic acid or sulfur trioxide-pyridine in various solvents including pyridine. The use of the ammonium salt of the sucrose polysulfate intermediate is not described here. The second stage of the prior art process involves the reaction of a sucrose polysulfate or its alkali metal salt with a source of aluminum ion at a pH range of from 3.5-5.5, especially preferred 4-4.5, see Column 2, lines 33-34.
The complex products described in this reference are reported to be impure. Note the wide range of analytical values at column 1, line 20 and line 54 of the U.S. Pat. No. 3,432,489. A report on the chemical and biological relationships of sucralfate, which work must utilize the purest samples of drug available, by R. Nagashima et al., Arzneim. Forsch. 29 1668 (1979) reveals a large percentage of impurities. Examination of the elemental analyses reported by Nagashima suggests sucralfate content in the 70% range.
Other chemical methods to prepare sucralfate are reported in the art. Maruko, Japanese Patent No. 57/67595 (1982), discloses the preparation of sucrose polysulfate ammonium salt by sulfonation of sucrose with chlorosulfonic acid in formamide and, then, treatment of this impure ammonium salt with activated aluminum hydroxide to produce impure sucrose polysulfate basic aluminum salt. Japanese Patent No. 58/208294 (1983), describes the preparation of sugar polysulfate potassium salts with certain basic polyaluminum chlorides. Spanish Patent No. 519512 (1984), discloses the preparation of sucrose polysulfate sodium salt by treatment of sucrose with chlorsulfonic acid in pyridine and sodium hydroxide. This same patent further describes the conversion of sucrose octasulfate sodium salt to sucrose octasulfate aluminum salt by treatment with aluminum chloride.
Some of the above processes involve steps which are tedious and time consuming. Furthermore, these processes have the defect of low yield and undetermined purity of product. For example, the process of Japanese Patent No. 57/67595 produces impure sucrose polysulfate ammonium salt and consequently, impure aluminum complex product. Often the prior art processes give sucralfate products which do not demonstrate proper physical characteristics for full biological activity.